2018 Fiscal Year Final Research Report
Development of nuclear acid medicine by using tumor suppressive microRNA conjugated with high molecular nano-micelle
| Project/Area Number |
16K15691
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
榎田 英樹 鹿児島大学, 医歯学域医学系, 准教授 (80347103)
関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013)
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| Research Collaborator |
Yoshino Hirofumi
Matsushita Ryousuke
Miyamoto Kazutaka
Yonemori Masaya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ナノミセル / マイクロRNA |
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| Outline of Final Research Achievements |
Based on microRNA expression profile of drug-resistant renal cell carcinoma, miR-210-3p was downregulated and had tumor suppressive function via targeting TWIST1. miR-1271a was upregulated and had oncogenic function via targeting tumor suppressive BMPR1B.
Followed by, we established nano-micelle type drug delivery system (DDS) by conjugating unit polyion complexes (u-PIC) and chimera microRNA in which 10 base nucleotides from its 3 prime region were exchanged to DNA. When the DDSs with 40 nM of miRNAs were administrated to the cultured cancer cells, the concentration of each microRNA was elevated to 100 times or more than pre-administrations. Also, from 20 to 50% knockdown effect of each target genes and apoptosis induction were observed.
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| Free Research Field |
泌尿器腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
unit polyion complexes (u-PIC)は生体内で安定するキメラ型2重鎖miRNAを内包することが可能であり、ナノミセル型ドラッグデリバリーシステム（DDS）の開発に成功した。各miRNAは培養癌細胞に効率よく取り込まれて抗腫瘍効果を発揮することが確認できた。次の段階のin-vivo投与実験を経て将来の核酸医薬創薬に向けて有意義な情報を得ることが出来た。
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